Osteoarthritis is expected to reach epidemic proportions worldwide. One of the keys to prevention is to diagnose cartliage degenerative processes early enough for disease modifying treatment. Optical coherence tomography (OCT) is a novel imaging technology that can image human articular cartilage at microscopic resolutions without damaging or removing the tissue. Preliminary data shows that loss of OCT detectable cartilage form birefringence was predictive of potentially reversible early metabolic changes that have been implicated in the pathogenesis of osteoarthritis. The PI has also successfully used a clinical fiberoptic OCT system to assess the microstructure and form birefringence of human articular cartilage in vivo. The central hypothesis of this proposal is that OCT can be used clinically to improve arthroscopic diagnosis of early articular cartilage degeneration. Three related specific aims are proposed: (1) To test the hypothesis that OCT enhances the sensitivity and specificity of conventional arthroscopic diagnosis of early cartilage degeneration in humans. (2) To test the hypothesis that OCT detectable microstructural damage is prevalent in grossly normal appearing weight bearing cartilage of human subjects undergoing arthroscopy to treat degenerative meniscal tears. (3) To test the hypothesis that OCT can be used clinically to predict the development of progressive cartilage degeneration as determined by serial MRI after acute anterior cruciate ligament (ACL) injury. Accomplishing the proposed aims will introduce valuable new data on the early changes in human osteoarthritis as discernible by novel imaging technology (OCT), 3.0 T MRI, and conventional arthroscopy. Preliminary data shows that OCT can identify human cartilage degeneration prior to the development of irreversible changes. As such, the proposal is highly innovative and significant in that achieving the aims can provide the diagnostic capability to potentially support a clinical paradigm shift towards treatment of cartilage degenerative processes years before what is currently possible. Potential advantages of earlier treatment include the possibility of delaying or even preventing the onset of disabling osteoarthritis.